Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.

Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. PATIENTS AND METHODS: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. RESULTS: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. CONCLUSIONS: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

Trace analysis of therapeutic inertia and subsequent hemoglobin A1c outcomes in a 2-year cohort study.

OBJECTIVE: Our understanding of therapeutic inertia in diabetes care is incomplete in terms of an assessment across a nationwide population. The key objectives of this investigation were to measure therapeutic inertia and link this phenomenon to the important surrogate outcome of hemoglobin A1c (HbA1c) control in a nationwide cohort. PATIENTS AND METHODS: We performed a retrospective cohort study over 18 months. Laboratory and prescription data were collected for 41,948 patients (women: 53.1%) with diabetes who had at least two HbA1c results. The association between treatment intensity and glycemic control, using the change in HbA1c during the observation period, and whether the HbA1c outcome was greater than 9% were examined. RESULTS: Among the patients who exhibited a secondary HbA1c result exceeding 9%, 8,630 (78.26%) had undergone intensified therapy at the time of the index HbA1c measurement, and among these patients, the incidence ratio of the last HbA1c outcome exceeding 9% after 6 to 18 months was 0.779-fold (95% Cl 0.728 to 0.834) greater than those who had not received intensified therapy (p < .001). CONCLUSIONS: After tracking patient data for a particular period, we found that patients with diabetes who received intensified therapy achieved surrogate outcomes of HbA1c control that were more favorable.

A three-generation family cluster with COVID-19 infection: should quarantine be prolonged?

OBJECTIVES: Families are a transmission route for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of the close contact. Monitoring of the viral load will be a valuable method to reduce the optimal number of quarantine days, especially in presymptomatic and symptomatic carriers of their households. The traditional three-generation families living together are seen frequently in East Asia, including in Taiwan. STUDY DESIGN: We report on a family cluster with six individuals infected with coronavirus disease in Taiwan. METHODS: The current public policy in Taiwan is quarantine for at least 14 days, based on the incubation period, or until the patient has tested negative three days in a row using the SARS-CoV-2 reverse transcription polymerase chain reaction. Details on the onset date of clinical symptoms, throat swab conversion, and course of disease were collected from medical records retrospectively. RESULTS: In the household of this three-generation Taiwanese family, the infection rate was 60%. The ratio of males to females was 4:2, and the age range was 11-85 years. The prevalence of asymptomatic disease was 33.3% (2/6). The longest throat swab conversion time was 37 days, and the estimated course of disease from symptoms to first conversion of throat swab was 59 days. CONCLUSIONS: Large families, including three-generation families in a single dwelling, should be monitored when the index case is found. Presymptomatic and symptomatic family members could be quarantined for an appropriate duration which, in our experience, is 2 months.

Regulation of oncogenic KRAS signaling via a novel KRAS-integrin-linked kinase-hnRNPA1 regulatory loop in human pancreatic cancer cells.

Integrin-linked kinase (ILK) is a mediator of aggressive phenotype in pancreatic cancer. On the basis of our finding that knockdown of either KRAS or ILK has a reciprocal effect on the other's expression, we hypothesized the presence of an ILK-KRAS regulatory loop that enables pancreatic cancer cells to regulate KRAS expression. This study aimed to elucidate the mechanism by which this regulatory circuitry is regulated and to investigate the translational potential of targeting ILK to suppress oncogenic KRAS signaling in pancreatic cancer. Interplay between KRAS and ILK and the roles of E2F1, c-Myc and heterogeneous nuclear ribonucleoprotein as intermediary effectors in this feedback loop was interrogated by genetic manipulations through small interfering RNA/short hairpin RNA knockdown and ectopic expression, western blotting, PCR, promoter-luciferase reporter assays, chromatin immunoprecipitation and pull-down analyses. In vivo efficacy of ILK inhibition was evaluated in two murine xenograft models. Our data show that KRAS regulated the expression of ILK through E2F1-mediated transcriptional activation, which, in turn, controlled KRAS gene expression via hnRNPA1-mediated destabilization of the G-quadruplex on the KRAS promoter. Moreover, ILK inhibition blocked KRAS-driven epithelial-mesenchymal transition and growth factor-stimulated KRAS expression. The knockdown or pharmacological inhibition of ILK suppressed pancreatic tumor growth, in part, by suppressing KRAS signaling. These studies suggest that this KRAS-E2F1-ILK-hnRNPA1 regulatory loop enables pancreatic cancer cells to promote oncogenic KRAS signaling and to interact with the tumor microenvironment to promote aggressive phenotypes. This regulatory loop provides a mechanistic rationale for targeting ILK to suppress oncogenic KRAS signaling, which might foster new therapeutic strategies for pancreatic cancer.

Pattern analysis and variations in the utilization of antihypertensive drugs in Taiwan: a six-year study.

BACKGROUND: In the last few years there have been changed in the pattern of consumption of antihypertensive drugs in other countries. Factors causing this variability include differences in the effectiveness of detection, guidelines for the management of hypertension, and differences in national health insurance systems among countries. AIM: The aim of this study was to reveal patterns in the use of antihypertensive drugs in Taiwan over a six year period (2001 to 2006) and compare these results with data from other countries. MATERIALS AND METHODS: This study performed descriptive analysis of data from the National Health Insurance Research Database (NHIRD) of Taiwan, and compared these findings with similar findings from around the world. Quantities were standardized using the defined daily dose (DDD) per 1000 inhabitants per day (DID) in accordance with WHO anatomical therapeutic classification and DDD measurement methodology. RESULTS: The total number of DDDs prescribed in Taiwan increased from 0.66 billion in 2001 to 1.08 billion in 2006, representing 80.6 and 129.2 DID in 2001 and 2006, respectively. This indicates a significant increase in the prescription of antihypertensive drugs in Taiwan over this period. The average annual increase ranged from 10.7% for calcium channel blockers (CCBs) to 22.1% for angiotensin II receptor blockers (ARBs). All of these patterns were statistically significant (p < 0.05). The rapid increase in the use of ARBs resulted in its surpassing ACEIs with the second highest DID (21.9) in 2006. Though the proportional use of CCBs and ARBs has increased significantly, the use of thiazide diuretics remains low. CONCLUSIONS: The consumption of antihypertension drugs in Taiwan increased during the period studied and the highest average annual increases were for ARBs and CCBs. Overall consumption of antihypertension drugs also increased in other countries, but differences in the relative increase for each class of drug suggest that further study may be required to clarify the origins and causes.

The effect of early cardiac rehabilitation on health-related quality of life among heart transplant recipients and patients with coronary artery bypass graft surgery.

PURPOSE: To investigate the effect of an early postoperative outpatient cardiac rehabilitation program to health-related quality of life among heart transplantation recipients (HTR) and patients with coronary artery bypass graft (CABG) surgery. METHODS: The study included 45 clinically stable HTR (age: 47 ± 14 years; 36 men, 9 women) and 34 patients with CABG (age: 57.2 ± 12.5 years; 27 men, 7 women). HTR started rehabilitation 70 ± 33 days after transplantation; patients with CABG started training 36 ± 18 days after surgery. Patients participated in a 12-week supervised exercise training program three times per week. Each training session comprised 10 minutes of warm-up, 25 to 30 minutes of cycling or treadmill walking, and 10 minutes of cooldown. The exercise intensity was set at 50% to 80% of peak oxygen uptake (V̇O(2peak)) according to the patient's condition. The health-related quality of life of subjects was evaluated by the Medical Outcomes Trust 36-item health survey (SF-36) at baseline and upon the completion of rehabilitation. RESULTS: At baseline, the HTR group showed lower V̇O(2peak) than the CABG group, but the health-related quality of life was similar between the two groups. After training, both groups exhibited an increase of 3.6 mL·kg(-1)·min(-1) in V̇O(2peak) and improvement of physical component in health-related quality of life. The HTR group showed a significant increase of SF-36 scores in physical functioning (59.7 ± 18.9 to 77.0 ± 14.0), physical role (21.1 ± 34.1 to 38.3 ± 37.9), bodily pain (57.4 ± 24.3 to 73.6 ± 21.5), social functioning (63.6 ± 23.4 to 72.8 ± 22.1), emotional role (59.2 ± 43.7 to 76.3 ± 37.4), and mental health (67.1 ± 17.9 to 73.4 ± 14.6). The CABG group only exhibited increased scores in physical functioning (60.0 ± 22.9 to 73.4 ± 18.0), physical role (19.1 ± 24.9 to 27.9 ± 38.3), bodily pain (57.1 ± 20.0 to 70.3 ± 16.1), and social functioning (54.0 ± 21.3 to 69.9 ± 21.1). CONCLUSIONS: Early postoperative cardiac rehabilitation significantly improved physical capacity and quality of life among heart transplant recipients and patients with CABG. Additionally, HTR showed greater improvement in health-related quality of life than patients with CABG regardless of lower physical capacity.

SIGNAL REGULARITY-BASED AUTOMATED SEIZURE DETECTION SYSTEM FOR SCALP EEG MONITORING.

The purpose of the present study was to build a clinically useful automated seizure detection system for scalp EEG recordings. To achieve this, a computer algorithm was designed to translate complex multichannel scalp EEG signals into several dynamical descriptors, followed by the investigations of their spatiotemporal properties that relate to the ictal (seizure) EEG patterns as well as to normal physiologic and artifact signals. This paper describes in detail this novel seizure detection algorithm and reports its performance in a large clinical dataset.

Assessment of a scalp EEG-based automated seizure detection system.

OBJECTIVE: The purpose of this study was to evaluate and validate an offline, automated scalp EEG-based seizure detection system and to compare its performance to commercially available seizure detection software. METHODS: The test seizure detection system, IdentEvent™, was developed to enhance the efficiency of post-hoc long-term EEG review in epilepsy monitoring units. It translates multi-channel scalp EEG signals into multiple EEG descriptors and recognizes ictal EEG patterns. Detection criteria and thresholds were optimized in 47 long-term scalp EEG recordings selected for training (47 subjects, ∼3653h with 141 seizures). The detection performance of IdentEvent was evaluated using a separate test dataset consisting of 436 EEG segments obtained from 55 subjects (∼1200h with 146 seizures). Each of the test EEG segments was reviewed by three independent epileptologists and the presence or absence of seizures in each epoch was determined by majority rule. Seizure detection sensitivity and false detection rate were calculated for IdentEvent as well as for the comparable detection software (Persyst's Reveal®, version 2008.03.13, with three parameter settings). Bootstrap re-sampling was applied to establish the 95% confidence intervals of the estimates and for the performance comparison between two detection algorithms. RESULTS: The overall detection sensitivity of IdentEvent was 79.5% with a false detection rate (FDR) of 2 per 24h, whereas the comparison system had 80.8%, 76%, and 74% sensitivity using its three detection thresholds (perception score) with FDRs of 13, 8, and 6 per 24h, respectively. Bootstrap 95% confidence intervals of the performance difference revealed that the two detection systems had comparable detection sensitivity, but IdentEvent generated a significantly (p<0.05) smaller FDR. CONCLUSIONS: The study validates the performance of the IdentEvent™ seizure detection system. SIGNIFICANCE: With comparable detection sensitivity, an improved false detection rate makes the automated seizure detection software more useful in clinical practice.

Phase contribution of image potential on empty quantum well States in pb islands on the cu(111) surface.

We use scanning tunneling spectroscopy to explore the quantum well states in the Pb islands grown on a Cu(111) surface. Our observation demonstrates that the empty quantum well states, whose energy levels lie beyond 1.2 eV above the Fermi level, are significantly affected by the image potential. As the quantum number increases, the energy separation between adjacent states is shrinking rather than widening, contrary to the prediction for a square potential well. By simply introducing a phase factor to reckon the effect of the image potential, the shrinking behavior of the energy separation can be reasonably explained with the phase accumulation model. The model also reveals that there exists a quantum regime above the Pb surface in which the image potential is vanished. Moreover, the quasi-image-potential state in the tunneling gap is quenched because of the existence of the quantum well states.

Invasive differences among Porphyromonas gingivalis strains from healthy and diseased periodontal sites.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine any difference between Porphyromonas gingivalis isolates from periodontally healthy sites as compared to those from diseased sites with respect to the ability to invade host cells. MATERIAL AND METHODS: Subgingival plaque samples were obtained from periodontally healthy and diseased sites using paper points. P. gingivalis colonies were isolated and tested, using an antibiotic protection assay, for their ability to invade KB cells. P. gingivalis 381 and Escherichia coli MC1061 were used as controls. RESULTS: Mean values of 16.79 +/- 0.86 x 10(3) colony-forming units/mL and 26.14 +/- 2.11 x 10(3) colony-forming units/mL were observed in invasion assays for isolates from periodontally healthy and diseased sites, respectively. P. gingivalis present in diseased sites had significantly greater invasive abilities than strains isolated from healthy sites. No statistical difference was noted between male or female subjects concerning the degree of invasion; isolates from diseased sites from both genders had significantly greater invasion abilities than those from healthy sites. A significant correlation was found between the increased invasive capabilities of P. gingivalis isolates vs. an increased probing depth. CONCLUSION: The increased invasion noted with P. gingivalis isolates from diseased sites vs. healthy sites, and the increased invasive capabilities with increasing probing depth, indicate that P. gingivalis isolates have a varying ability to invade host cells in the periodontal pocket.

Factors influencing the successful treatment of infectious pulmonary tuberculosis.

SETTING: Achieving successful treatment of infectious pulmonary tuberculosis (PTB) could reduce the spread of tuberculosis (TB) and the emergence of multidrug resistance. OBJECTIVE: To explore factors associated with successful treatment for sputum-positive PTB. DESIGN: This study used a population-based retrospective cohort design. All PTB patients residing in southern Taiwan recorded in the tuberculosis registry from 1 January to 30 June 2003 were identified. Each patient's medical record was requested from treating hospitals and retrospectively reviewed for 15 months after the date PTB was confirmed. RESULTS: There were 399 PTB patients included in the study. Factors significantly associated with successful treatment included treatment by pulmonologists (OR 1.93), receiving directly observed therapy (DOT) (OR 1.76) and receiving treatment at the chest hospital (OR 5.41). Patients of advanced age were less likely to achieve treatment success (OR 0.97). Among patients treated by pulmonologists, those treated at the chest hospital had a significantly higher treatment success rate than those treated at other institutions (94.1% vs. 69.9%). CONCLUSIONS: Patients treated with DOT and by pulmonologists, especially at the chest hospital, had a higher treatment success rate. DOT and training of care professionals and institutions are therefore important factors that affect the successful treatment of TB.

A novel conformation-dependent monoclonal antibody specific to the native structure of beta-lactoglobulin and its application.

Molten globules are thought to be general intermediates in protein folding and unfolding. beta-lactoglobulin (beta-LG) is one of the major bovine whey proteins, constituting approximately 10 to 15% of total milk proteins. We have recently identified beta-LG as a superior marker for evaluating thermally processed milk. Strand D of beta-LG participates in irreversible thermal unfolding as probed by a monoclonal antibody (mAb) specific to thermally denatured beta-LG. In the present study, we used native beta-LG as an immunogen to test the hypothesis that a specific mAb against the native beta-LG could be established. As result, a mAb (4H11E8) directed against the native structure of beta-LG was made. The antibody did not recognize the heat-denatured form of beta-LG, such as its dimer and aggregates. Immunoassay using this "native" mAb showed that the stability of beta-LG was at temperatures < or =70 degrees C. beta-Lactoglobulin began to deteriorate between 70 and 80 degrees C over time. The denaturation was correlated with the transition temperature of beta-LG. Further chemical modification of Cys (carboxymethylation) or positively charged residues (acetylation) of beta-LG totally abolished its immunoreactivity, confirming the conformation-dependent nature of this mAb. Using competitive ELISA, the 4H11E8 mAb could determine the native beta-LG content in commercially processed milks. Concentrations of native beta-LG varied significantly among the local brands tested. From a technological standpoint, the mAb prepared in this study is relevant to the design and operation of appropriate processes for thermal sanitation of milk and of other dairy products.

Effect of conjugated linoleic acid immobilization on the hemocompatibility of cellulose acetate membrane.

Conjugated linoleic acid (CLA) was covalently immobilized onto cellulose acetate (CA) membranes. The effects of CLA immobilization on the blood coagulation, platelet aggregation, and oxidative stress were evaluated using human blood. The resulting CLA grafting CA membranes were characterized with X-ray photoelectronic spectroscopy (XPS). The complete blood count (CBC) and coagulation time (CT) was evaluated in vitro for the hemocompatibility. Human serum albumin (HSA) and human plasma fibrinogen (HPF) was evaluated for the protein affinity. The production of reactive oxygen species (ROS) was measured by chemiluminescence (CL) method to evaluate the oxidative stress. The results showed that the CLA-immobilizing CA membrane could keep the CBC values more stable than unmodified CA membrane. The CLA-immobilized CA membranes also showed longer CT and less adsorption of plasma proteins. CLA-immobilized CA membrane could keep the CL counts of hydrogen peroxide and superoxide values more stable than unmodified CA membrane. These results suggest that a CLA-immobilized CA membrane could offer protection for patients against oxidative stress and would be helpful for reducing the dosage of anticoagulant during hemodialysis.

Smoking attributable medical expenditures, years of potential life lost, and the cost of premature death in Taiwan.

OBJECTIVE: To estimate the smoking attributable medical expenditures and productivity loss of people aged 35 and over in Taiwan in 2001 from a societal viewpoint. METHODS: A prevalence based approach was used to estimate smoking attributable costs. Epidemiological parameters were obtained from two follow up studies and government statistics. Data on medical care utilisation and expenditure were extracted from the National Health Insurance claim data. RESULTS: Total smoking attributable medical expenditures (SAEs) amounted to USD 397.6 million, which accounted for 6.8% of the total medical expenditures for people aged 35 and over. Mean annual medical expenditures per smoker was USD 70 more than that of each non-smoker. Smoking attributable years of potential life lost (YPLL) totalled to 217,761 years for males and 15,462 years for females, and the corresponding productivity loss was USD 1371 million for males and USD 18.7 million for females. CONCLUSION: Medical expenditures attributable to smoking accounted for 6.8% of the total medical expenditure of people aged 35 and over for the year 2001 in Taiwan. Corresponding YPLL and productivity loss also demand that actions be taken to fight cigarette smoking.

Acute mediastinitis resulting from an unsuspected fish bone--case report.

Acute mediastinitis is a serious medical condition with a mortality rate from 30 to 40% or even higher. Early diagnosis with prompt and aggressive treatment is essential to prevent its rapid progression. Severe odynophagia and respiratory distress with positive neck or chest findings should raise suspicion of mediastinitis. We report a rare case of acute mediastinitis secondary to the unexpected migration of an impacted fish bone from the esophagus.